Project Summary The cerebellum is essential for producing skilled movements, like reaching, and dysfunction of this structure causes disruptive motor disorders. However, how cerebellar output influences the structures that command skilled motor output remains unclear. Cerebellum targets the red nucleus (RN), a brainstem pre-motor nucleus that is known to command movements of the limbs. Previous research in my lab has shown that modest optogenetic activation of the interposed nucleus of the cerebellum (IN) results in a kinematic perturbation of the forelimb in mice performing reaching movements12. Strikingly, the properties of the observed perturbation are context-dependent, but phase-independent, e.g. there is no movement at rest, and the same change in movement occurs both in outreach and return of the paw. These findings lead me to hypothesize that cerebellar output is interpreted differentially downstream depending on context and phase, and that RN is a site that mediates differential effects of cerebella output. To test this hypothesis, I will record neural activity in RN during differing phases of reach and at rest while activating IN optogenetically. This will allow me to examine if IN activation differential effect on RN activity between contexts and phases. Additionally, I will record the activity of muscles of the forelimb during IN activation to determine if the effect on muscle activation is dependent on context and phase. I expect to find that both RN activity and EMG amplitude will be reduced during rest, different between phases, and that the observed changes will aid in explaining the observed context-dependence and phase-invariance. I will also establish the degree of necessity of the cerebellorubral circuit in mediating these effects through the expression of excitatory and inhibitory designer receptors in RN, that, when paired with IN stimulation optogenetically, should reveal the input output relationship between IN, RN, and the effected kinematics due to the cerebellorubral motor pathway.